This case-control study assesses relations of human papillomavirus (HPV) type 16 infection, sexual history, cigarette smoking, and oral contraceptive use to low- and high-grade cervical intraepithelial neoplasia (CIN). A total of 548 high-grade and 338 low-grade CIN cases and 612 controls were identified among women seen at a colposcopy clinic in Quebec, Quebec, Canada, in 1988-1989. Interviews, colposcopy, cervical scrapings, and colposcopically directed biopsies were performed. One pathologist reviewed all histologic slides. Southern blot techniques were used to assay specimens for HPV 16 DNA. Lifetime number of sexual partners was related to low- and high-grade CIN. Presence of HPV 16 DNA was associated with a 8.7-fold (95% confidence interval 5.1-15.0) elevation in estimated relative risk of high-grade CIN. Relative risk of high-grade CIN increased with amount of HPV 16 DNA (p < 0.0001). Estimated relative risk of high-grade CIN in current cigarette smokers was 2.4 (95% confidence interval 1.8-3.2) compared with never smokers and increased with number of pack-years of exposure (p < 0.0001). Long-term (6 years or more) users of oral contraceptives had an estimated relative risk of high-grade CIN of 1.9 (95% confidence interval 1.1-3.3) compared with those who never used such contraceptives. In contrast, presence of HPV 16 DNA, cigarette smoking, and oral contraceptive use showed little or no relation to low-grade CIN. Risk factors for low- and high-grade CIN may differ substantially.